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Gang Liu, PhD
Postdoctoral Research Fellow
Department of Nutrition
Harvard T.H. Chan School of Public Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Although many approaches can be used to achieve a short-term weight loss, maintenance of weight loss has become a key challenge for sustaining long-term benefits of weight loss. Accumulating evidence has suggested that certain environmental compounds may play an important role in weight gain and obesity development.

The potential endocrine-disrupting effects of perfluoroalkyl substances (PFASs), which are extensively used in many industrial and consumer products including food packaging, paper and textile coatings, and non-stick cookware, have been demonstrated in animal studies, but whether PFASs may interfere with body weight regulation in humans is largely unknown.

In a 2-year POUNDS Lost randomized clinical trial that examined energy-restricted diets on weight changes, baseline plasma concentrations of major PFASs were measured among 621 overweight and obese participants aged 30-70 years. Body weight was measured at baseline, 6, 12, 18, and 24 months. Resting metabolic rate (RMR) and other metabolic parameters, including glucose, lipids, thyroid hormones, and leptin, were measured at baseline, 6, and 24 months.

We found that higher baseline levels of PFASs were significantly associated with a greater weight regain, primarily in women. On average, women in the highest tertile of PFASs regained 1.7-2.2 kg more body weight than women in the lowest tertile. In addition, higher baseline plasma PFAS concentrations, especially perfluorooctanesulfonic acid (PFOS) and perfluorononanoic acid (PFNA), were significantly associated with greater decline in RMR during the first 6 months and less increase in RMR during weight regain period.Continue reading →

Varykina Thackray, Ph.D.Associate Professor of Reproductive Medicine
University of California, San Diego

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies have shown that changes in the composition of intestinal microbes (gut microbiome) are associated with metabolic diseases. Since many women with polycystic ovary syndrome (PCOS) have metabolic dysregulation that increases the risk of developing type 2 diabetes and cardiovascular disease, we wondered whether PCOS was associated with changes in the gut microbiome and if these changes were linked to any clinical features of PCOS.

We collaborated with Beata Banaszewska and her colleagues at the Poznan University of Medical Sciences in Poznan, Poland to obtain clinical data and fecal samples from 163 premenopausal women recruited for the study. In collaboration with Scott Kelley at San Diego State University, we used 16S ribosomal RNA gene sequencing and bioinformatics analyses to show that the diversity of the gut microbiome was reduced in Polish women with PCOS compared to healthy women and women with polycystic ovaries but no other symptoms of PCOS.

The study confirmed findings reported in two other recent studies with smaller cohorts of Caucasian and Han Chinese women. Since many factors could affect the gut microbiome in women with PCOS, regression analysis was used to identify clinical hallmarks that correlated with changes in the gut microbiome. In contrast to body mass index or insulin resistance, hyperandrogenism was associated with changes in the gut microbiome in this cohort of women, suggesting that elevated testosterone may be an important factor in shaping the gut microbiome in women.

Response: The palbociclib/letrozole combination therapy was granted accelerated approval by the U.S. Food and Drug Administration in 2015 after a clinical trial showed it doubled the progression-free survival time in postmenopausal women with estrogen receptor (ER) positive, metastatic breast cancer. Letrozole blocks the production of estrogen, thus reducing the growth-promoting stimulation of ERs on breast cancer cells. Palbociclib blocks a different signaling pathway to impede cell division. The combination is now one of the standard therapies for ER-positive breast cancers.

The aim of our study was twofold:

Firstly, we investigated the drugs synergism at the metabolome level in MCF-7 cells to unravel the unknown underlying metabolic effects of palbociclib/letrozole mechanism of action. We used a global metabolomics approach to analyze the effects of palbociclib and letrozole individually and in combination on breast cancer cells. Metabolomics studies detail cells’ metabolomes—populations of metabolites, the small-molecule end products of cellular processes.

Secondly, we aimed at deciphering the impact of the two model xenoestrogens frequently present in our diet, zearalenone and genistein, on this chemotherapy. Since these chemicals interact with the estrogen receptor we hypothesized that they may interfere with the new treatment. Continue reading →

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: USPSTF recommendations are based off several studies, but is mainly based off of the Women’s Health Initiative.

The Women’s Health Initiative was a 15 year prevention study with a focus on death, disability and impaired quality of life in postmenopausal women. This study was originally performed in 1991.

The USPSTF reevaluated the data along with several other studies to assess the role of hormone replacement therapy in prevention of chronic diseases such as heart disease, stroke, blood clot, gallbladder disease, dementia. The USPSTF has found that hormone replacement therapy has some benefit in reducing the risk of fractures, and, potentially, diabetes. The USPSTF has found that hormone replacement therapy can increase the risk of coronary artery disease, stroke, blood clot, gall bladder disease, urinary incontinence and dementia.

With these risks, the USPSTF states that hormone replacement therapy should not be used as a preventative medicine, but, rather, used for treatment of symptomatic menopause and not prevention of osteoporosis or heart disease.

 Women who test positive for thyroid autoantibodies have been reported to be at 2- to 3-fold higher risk of spontaneous miscarriage than those who test negative. However, the effect of levothyroxine on miscarriage among women with positive thyroid autoantibodies and normal thyroid function has been documented in limited studies with conflicting results.

 Given the substantial difficulty achieving successful pregnancy among infertile women, identifying optimal treatment for infertile women who test positive for thyroid autoantibodies is particularly important. There are a few randomized clinical trials showing a beneficial effect of levothyroxine treatment on pregnancy outcomes among women undergoing in vitro fertilization and embryo transfer (IVF-ET). However, the sample size of those trials was rather small which may weaken the quality of the evidence.

 Therefore, the Pregnancy Outcomes Study in euthyroid women with Thyroid Autoimmunity after Levothyroxine (POSTAL) study was conducted in Peking University Third Hospital to evaluate whether levothyroxine treatment initiated before IVF-ET could decrease the miscarriage rate and improve the live birth rate in infertile women who tested positive for antithyroperoxidase antibody but had normal thyroid function.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Osteoporosis is a significant public health burden, with origins early in life. Later puberty and lower adolescent bone mineral density are both risk factors for osteoporosis.

Geneticists have identified hundreds of genetic variants across the genome that impact pubertal timing, and we found that collectively this variation also plays a role in bone mineralization during adolescence. Additionally, we found that later puberty caused lower adult bone density.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: ​Previous research has shown that estradiol treatment after menopause can reduce the stress response when exposed to a stressor, including the cortisol response to stress. Other work has shown that stress can impair certain types of memory​. We wanted to test whether post-menopause estradiol treatment would not only attenuate the cortisol response to stress, but if it could also reduce the negative effects of stress on memory. In particular, we tested the effects on a type of memory called working memory. Working memory allows us to maintain and update information we need to readily access in short-term memory. For example, imagine you stop at the grocery store after work and only have a mental list of the items you need to make dinner. Working memory is the memory type engaged in helping you maintain and update your mental list of items as you grab items off the shelves and check them off your list.

We recruited women through the Early versus Late Intervention Trial with Estradiol, a randomized, double-blinded, placebo-controlled clinical trial. Women who participated in our study had received nearly 5 years of either estradiol or placebo.

We found that women receiving estradiol showed significantly smaller cortisol responses to stress and less of an effect of stress on working memory than women that had been receiving placebo.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: For the past two decades, D. Samba Reddy, PhD, RPh, professor of neuroscience and experimental therapeutics at the Texas A&M College of Medicine, has been searching for answers to catamenial epilepsy, a subset of chronic epilepsy that causes a dramatic increase in seizures during women’s menstrual periods. Although this condition has been documented for millennia, there is currently no effective treatment for catamenial seizures, leaving many women and their families desperate for answers.

In this report, the researchers discovers the neuro-code for treating women with menstrual period-linked epilepsy. A unique platform has been created for clinical trials for catamenial seizures with synthetic neurosteroid agents.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Thyroid function is clinically defined by the measurements of serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels. So far, abnormal TSH and FT4 levels as well as variations within the normal range have been linked to an increased risk of cardiovascular disease and death. However, it remains unclear whether there are differences in life span and years of life lived with and without cardiovascular disease, within the reference range of thyroid function. To investigate this, we performed a prospective study among 7785 middle-aged and elderly people with normal thyroid function. Participants were part of the Rotterdam Study, 65 years on average and 52% females. In our statistical analyses, we accounted for sociodemographic and cardiovascular risk factors. Over a median follow-up of 8.1 years, 789 incident cardiovascular deaths and 1357 deaths occurred. Analyses were performed separately among men and women.

Our study found differences in life expectancy within the reference range of thyroid function. At the age of 50 years, people with low-normal thyroid function lived up to 3.5 years longer than those with high-normal thyroid function. Also, people with low-normal thyroid function lived a longer life without cardiovascular disease than those with high-normal thyroid function.

Response: The current report provides new information on total mortality and the rates of death from specific causes (cardiovascular disease, cancer, other major illnesses) over 18 years of follow-up in the Women’s Health Initiative (WHI) randomized trials of hormone therapy (estrogen + progestin and estrogen alone). This is the first WHI report to focus on all-cause and cause-specific mortality. It includes all of the 27,347 women in the 2 hormone therapy trials with >98% follow-up over 18 years, during which time 7,489 deaths occurred. This is more than twice as many deaths as were included in earlier reports. The report also provides detailed information on differences in results by age group (ages 50-59, 60-69, 70-79) at time of study enrollment.

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